DALLAS Feb. 17, 2011 Low levels of the anti-aging hormone Klotho may serve as an early warning sign of the presence of kidney disease and its deadly cardiovascular complications, according to findings by UT Southwestern Medical Center researchers.
Using mice, investigators found that soft-tissue calcification, a common and serious side effect of chronic kidney disease (CKD), improves when Klotho hormone levels are restored. The study is available online in the Journal of the American Society of Nephrology.
The essential Klotho protein, which is produced by the kidneys, often plummets in CKD. This may explain why supplementing Klotho levels helps counteract a major side-effect associated with the disease, said Dr. Orson Moe, director of the Charles & Jane Pak Center for Mineral Metabolism and Clinical Research at UT Southwestern and the senior author of the study.
Mice with chronic kidney disease exhibit low levels of Klotho in their kidneys, blood and urine, indicating that CKD is a state of systemic Klotho deficiency, Dr. Moe said. In the study, researchers also tested urine from 53 human participants, including 40 CKD patients, and found that they also had low levels of the essential protein.
"It can be a vicious cycle, where CKD begets low Klotho and low Klotho accelerates CKD," Dr. Moe said. "Chronic kidney disease appears to go hand-in-hand with chronic Klotho deficiency. Animal studies have shown that a dangerous consequence of inadequate Klotho is soft-tissue calcification, which can interfere with normal organ function."
In the current study, UT Southwestern researchers decreased Klotho levels in mice by genetically engineering them to produce inadequate levels of the protein. Restoring adequate Klotho levels to the rodents with CKD markedly improved renal function and blood chemistry and reduced vascular calcification.
In contrast, mice with CKD that were genetically engineered to have ab
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UT Southwestern Medical Center